| 21. |
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| 22. |
- Ciulla, M. M., et al.
(författare)
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Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: results of a randomized trial
- 2004
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Ingår i: Circulation. - 1524-4539. ; 110:5, s. 552-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis. METHODS AND RESULTS: We compared the effects of an angiotensin II receptor antagonist with a beta-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.5 to 25 mg/d for 36 weeks. Echoreflectivity analysis was conducted on ultrasound tracings of the midapex septum with specifically designed and validated software. A color histogram of reflecting echoes was obtained, and its spread (broadband [BB], previously shown to correlate directly with collagen volume fraction on endomyocardial biopsies) was used as the primary outcome measure. Mean color scale and serum markers of collagen synthesis (PIP, PIIIP) or degradation (CITP) were secondary outcome variables. Echoreflectivity analysis proved feasible in 106 patients (losartan 52, atenolol 54). Losartan reduced BB over 36 weeks (from 114.5 to 104.3 color levels, P<0.02), whereas atenolol treatment was associated with an increase in BB (from 109.0 to 113.6 color levels, P=NS), the difference between treatments being -12.8 color levels (95% CI -23.6 to -2.0, P=0.02). Secondary end points (mean color scale and collagen markers) also changed in the direction of decreased collagen in patients receiving losartan, but differences between groups were not statistically significant. CONCLUSIONS: In hypertensive patients with LVH, losartan decreases myocardial collagen content, whereas atenolol does not. The difference between the 2 treatments is statistically significant.
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| 23. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Addition of the calcium antagonist PN 200-110 to pindolol markedly augments the antihypertensive effect in essential hypertension.
- 1987
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 10 Suppl 10, s. S102-4
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Tidskriftsartikel (refereegranskat)abstract
- Several large-scale studies have recently drawn attention to the fact that arterial hypertension frequently is inadequately controlled and that therapeutic alternatives other than the commonly employed stepped-care treatment may be needed in order to obtain normotension. For this reason PN 200-110, a new dihydropyridine calcium antagonist--at two different dose levels (average 3.8 mg b.i.d. or 5.7 mg b.i.d.)--or placebo was added in a double-blind cross-over trial to pindolol, 10 mg per day, in 20 patients with essential hypertension, after an initial 3-week placebo period. Ionized calcium in serum was determined repeatedly during the study. From an initial level of 157/100 mm Hg, PN 200-110 at the first dose level reduced blood pressure by 14/11 mm Hg (p less than 0.01/0.001) and at the second dose level reduced blood pressure by 22/18 mm Hg (p less than 0.001/0.001). The reduction in mean arterial pressure was significantly correlated to age (=0.050, p less than 0.05). There was no significant increase in heart rate, nor were there any significant correlations between ionized calcium and the effect of PN 200-110 nor between the changes in ionized calcium and the changes in blood pressure. Adverse effects were few and mild. One patient had to be withdrawn because of side effects, probably not related to the investigated drugs. Thus, addition of PN 200-110 to hypertensive patients treated with pindolol caused highly significant and clinically relevant further reductions in arterial pressure. The results show that a combination of this kind offers the possibility of good blood pressure control.
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| 24. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Atenolol as a comparator in outcome trials in hypertension: a correct choice in the past, but not for the future?
- 2007
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Ingår i: Blood Press. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 16:1, s. 6-12
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Twelve years after the design of the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which showed superiority of losartan- vs atenolol-based therapy for cardiovascular outcomes, we reviewed the literature for the effect of beta-blockers compared with initial placebo or no treatment on reduction of cardiovascular events to re-evaluate atenolol as the comparator in the LIFE study. METHODS: A literature search was conducted in September 2006 for randomized, controlled trials comparing beta-blockers with/without diuretics with placebo or no treatment in patients with hypertension and without recent cardiovascular morbidity. We calculated risk reductions for combined cardiovascular events, cardiovascular death, stroke, and coronary heart disease from groups of trials using atenolol first-line and all beta-blockers first-line. RESULTS: Five studies met the criteria. Significant risk reductions for cardiovascular events and stroke occurred in groups receiving treatment with atenolol or all beta-blockers, and for cardiovascular death in the all beta-blocker analysis. In meta-analysis of beta-blocker vs placebo or no treatment trials, risk reductions were 19% for combined cardiovascular events (95% CI 0.73-0.91, p<0.001), 15% for cardiovascular death (0.73-0.99, p = 0.037), 32% for stroke (0.57-0.82, p<0.001), and 10% for coronary heart disease (0.78-1.04, p = 0.146). CONCLUSIONS: Beta-blocker-based antihypertensive therapy significantly reduces cardiovascular risk in hypertension compared with placebo or no treatment. Atenolol was an appropriate comparator in the LIFE study. As the results of the LIFE study and other recent trials demonstrate superiority of newer agents over atenolol, this agent is not an appropriate reference drug for future trials of cardiovascular risk in hypertension.
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| 25. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Calcium antagonists combined with beta-blockers or ACE inhibitors in the treatment of hypertension.
- 1988
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Ingår i: Journal of cardiovascular pharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0160-2446. ; 12 Suppl 6, s. S104-8
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Tidskriftsartikel (refereegranskat)abstract
- During the last few years, there has been a growing awareness that treated hypertensive patients are still at substantially increased risks for cardiovascular morbidity and mortality and that one conceivable explanation for this is that their blood pressure has not been lowered to strictly normotensive levels. To obtain normotensive blood pressures, it may be necessary to skillfully combine antihypertensive drugs much more frequently than has been common so far. In this context, calcium antagonists in combination with beta-blockers are of special interest, since several controlled studies have shown that a combination between a beta-blocker and nifedipine, nitrendipine, isradipine, or felodipine have been remarkably potent as regards their antihypertensive effect. In controlled trials, such combinations have also been shown to be more effective and better tolerated than a combination between a beta-blocker and hydralazine. Marked efficacy has also been noted when a calcium antagonist has been combined with an angiotensin converting enzyme (ACE) inhibitor. So far, most studies have dealt with small numbers of patients and study design has not always been optimal. Results from controlled studies will presumably be ready for presentation in the near future. It can be concluded that combination therapy between calcium antagonists and beta-blockers or ACE inhibitors appear to be markedly effective and well tolerated. This would offer the possibility of reducing elevated arterial pressure to normotensive levels in many hypertensive patients.
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| 26. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Felodipine-metoprolol combination tablet: maintained health-related quality of life in the presence of substantial blood pressure reduction
- 2005
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Ingår i: Am J Hypertens. - : Oxford University Press (OUP). - 0895-7061. ; 18:10, s. 1313-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most treated hypertensive patients do not achieve adequate blood pressure (BP) control. Initiating therapy with two drugs has been suggested when BP is >20/10 mm Hg above goal. To ensure patients' compliance, such treatment needs to be well tolerated and must not compromise health-related quality of life (HRQL). The primary objective of this study was to compare the effects on HRQL of initiating treatment with felodipine + metoprolol (F+M) fixed combination tablets, or enalapril (E), or placebo (P). METHODS: A total of 947 patients of both sexes with primary hypertension (diastolic BP 95 to 110 mm Hg), aged 20 to 70 years, participated in this randomized, double-blind, parallel group, 12-week, multicenter trial. Treatment was initiated with F+M 5 + 50 mg, or E 10 mg, or P. Doses were doubled after 4 or 8 weeks if diastolic BP was >90 mm Hg. The HRQL was measured at baseline and at the last visit using two validated questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptom Assessment Profile (SSA-P). Office BP was measured at trough, that is, 24 h after the previous dose. RESULTS: The HRQL was high at baseline and generally well maintained during the study. For example, the mean (SD) PGWB total score was 104 (16) at baseline and 105 (16) at 12 weeks in all three treatment groups. The BP reductions after F+M (18/14 mm Hg) and E (12/9 mm Hg) were significantly greater than after P (7/7 mm Hg), and the reduction after F+M was significantly greater than after E. CONCLUSIONS: The HRQL is maintained in the presence of substantial BP reduction during antihypertensive treatment with F+M fixed combination tablets.
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| 27. |
- Dahlöf, Björn, 1953
(författare)
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Further evidence for low-dose combinations in patients with left ventricular hypertrophy
- 2005
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Ingår i: J Hum Hypertens. - 0950-9240. ; 19 Suppl 1, s. S9-14
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Tidskriftsartikel (refereegranskat)abstract
- Left ventricular hypertrophy (LVH) is a powerful independent risk predictor for cardiovascular disease and reversal of LVH has become a primary goal of antihypertensive management. Recent evidence has confirmed that most hypertensive patients will benefit from a low-dose combination strategy to manage their hypertension, and two trials have recently examined the effect of this strategy on left ventricular mass. The REASON study (pREterax in regression of Arterial Stiffness in a contrOlled double-bliNd study) compared the low-dose combination of an angiotensin-converting enzyme (ACE) inhibitor and a diuretic with beta-blocker monotherapy in hypertensive patients with LVH, and the PICXEL study (Preterax In a double-blind Controlled study versus Enalapril in LVH) compared the same low-dose combination with ACE inhibitor monotherapy in hypertensive patients with echocardiographic LVH. The REASON study demonstrated that the low-dose combination produced a significantly greater change in left ventricular mass after 1 year than the beta-blocker, despite inducing a similar change in mean blood pressure. Additionally, perindopril/indapamide reduced central (carotid) and peripheral (brachial) systolic blood pressure (SBP) and pulse pressure (PP) to a significantly greater extent than beta-blocker, and these benefits were more pronounced for the central values; LVH is affected more by central rather than peripheral haemodynamic changes. Results of the analysis of the PICXEL study showed a significantly greater decrease in LVH parameters and blood pressure over 1 year in favour of the low-dose combination. This reduction cannot be entirely explained by the better efficacy of the low-dose combination on blood pressure reduction.
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| 28. |
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| 29. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Introduction
- 2005
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Ingår i: Acta Diabetol. - 0940-5429. ; 42 Suppl 1, s. S1-2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 30. |
- Dahlöf, Björn, 1953, et al.
(författare)
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Perindopril/indapamide combination more effective than enalapril in reducing blood pressure and left ventricular mass: the PICXEL study
- 2005
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Ingår i: J Hypertens. - 0263-6352. ; 23:11, s. 2063-70
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Few data are available comparing the effects of monotherapy and combination therapy on target organ damage. The PICXEL study compared the efficacy of a strategy based on first-line combination with perindopril/indapamide versus monotherapy with enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. METHODS: In this 1-year multicentre randomized double-blind study, patients received an increasing dosage of perindopril/indapamide (n = 284) or enalapril (n = 272). Changes in blood pressure and echocardiographic measures of LVH were assessed from baseline to the end of treatment. Reading of the echocardiograms was central and blinded for therapy, patient and sequence. RESULTS: Systolic and diastolic blood pressure decreased significantly more in the perindopril/indapamide than in the enalapril group (P < 0.0001 and P = 0.003). The left ventricular mass index decreased by 13.6 +/- 23.9 g/m(2) (mean +/- SD) with perindopril/indapamide (P < 0.0001) and 3.9 +/- 23.9 g/m(2) with enalapril (P < 0.005); these decreases were significantly different (P < 0.0001). The left ventricular internal diameter, posterior and interventricular septal wall thickness decreased significantly with perindopril/indapamide (P < or = 0.0001); the interventricular septal wall thickness decreased significantly with enalapril (P < 0.001). Both treatments were well tolerated. CONCLUSION: A strategy based on first-line combination with perindopril/indapamide achieved better blood pressure decrease with a significantly greater degree of LVH reduction than a strategy based on monotherapy with enalapril in hypertensive patients with LVH.
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